MUTATIONAL PROCESSES OF SIMPLE-SEQUENCE REPEAT LOCI IN HUMAN-POPULATIONS
MUTATIONAL PROCESSES OF SIMPLE-SEQUENCE REPEAT LOCI IN HUMAN-POPULATIONS
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DOI：
10.1073/pnas.91.8.3166
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发表时间：
1994-04-12
影响因子：
11.1
通讯作者：
FREIMER, NB
中科院分区：
文献类型：
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作者：
DIRIENZO, A;PETERSON, AC;FREIMER, NB
人们对复杂基因组中简单序列重复（SSR）的突变过程知之甚少。我们通过引入两阶段突变模型来检查这些过程。在这个模型中，大多数突变都是单步变化，但重复次数也会出现罕见的大幅跳跃。我们使用计算机模拟来确定统计数据的预期值，这些值反映了两相模型和两种替代模型（一步模型和几何模型）的等位基因大小的频率分布。通过与撒丁岛人群中基因分型的 10 个 SSR 位点的观测值进行比较，测试了每个模型的理论预期，撒丁岛人群的遗传和人口统计历史先前已被重建。两阶段模型提供了最适合该人群中大多数基因座的数据。在分析中，我们假设基因座是中性的，并且该种群经历了快速的种群增长。最近对不稳定三核苷酸重复的观察结果支持了我们的建议，即重复次数的频繁小变化和罕见的大变化代表了 SSR 位点的两种不同类型的突变。我们对埃及和撒哈拉以南非洲样本中相同的 10 个基因座进行了基因分型，以评估 SSR 在研究种群差异方面的效用，并发现 SSR 的种群间距离估计值与线粒体 DNA 分析得出的估计值相似。
Mutational processes of simple sequence repeats (SSRs) in complex genomes are poorly understood. We examined these processes by introducing a two-phase mutation model. In this model, most mutations are single-step changes, but infrequent large jumps in repeat number also occur. We used computer simulations to determine expected values of statistics that reflect frequency distributions of allele size for the two-phase model and two alternatives, the one-step and geometric models. The theoretical expectations for each model were tested by comparison with observed values for 10 SSR loci genotyped in the Sardinian population, whose genetic and demographic histories have been previously reconstructed. The two-phase model provided the best fit to the data for most of these loci in this population. In the analysis we assumed that the loci were neutral and that this population had undergone rapid population growth. Recent observations made for unstable trinucleotide repeats support our suggestion that frequent small changes and rare large changes in repeat number represent two distinct classes of mutation at SSR loci. We genotyped the same 10 loci in Egyptian and sub-Saharan African samples to assess the utility of SSRs for studying the divergence of populations and found that estimates of interpopulation distances from SSRs were similar to those derived from analysis of mitochondrial DNA.